This grant is for the continuation of the work to utilize specialized digital-computer techniques for the completely automatic investigation of chromosome karyograms. The specific aims are as follows: (a) extend automatic computer chromosome-spread detection methods to all types of banding stains, and improve the "good spread" detection rate; (b) perfect the banding analysis computer programs; (c) extend banding-analysis computer programs to cover new types of banding methods as they arise; (d) investigate the quantitative relationships between different types of banding patterns, utilizing the computer programs; (e) write programs to identify trisomes, translocations, and other abnormalities through banding analysis; (f) apply automatic computer banding analysis to aid in hybrid-cell experiments; (g) analyze the technical parameters of the methods; (h) study human cytogenetic variables and establish detailed quantitative normative data for G, Q, C, and R banding (and other banding stains as they are developed). We shall investigate homologue variation, within-person variation (i.e., variation between cells of the same person), and between-person variation (i.e., variation between cells of different people). In addition, we shall study the incidence of polymorphisms, translocations, trisomes, and other abnormalities; (i) perform special studies in human cytogenetics. These studies will include investigations involving antenatal cells and fibroblasts. We shall analyze banded chromosomes from different laboratories to detect any systematic differences. And finally, we shall study families to see if banding polymorphisms and technical parameter values are inherited traits, i.e., are more consistent within a family than between families. The results of these investigations will be applied to screening high-risk women; screening newborns by means of the amnion, or birth membrane; giving genetic counseling to individuals with family histories of mental retardation and other known cytogenetic abnormalities; and monitoring the effects of low levels of radiation and environmental pollutants on human chromosomes.